tbuckley/cabot-search huggingface dataset:
Bone Biomarkers and Subsequent Survival in Men with Hormone-sensitive Prostate Cancer: Results from the SWOG S1216 Phase 3 Trial of Androgen Deprivation Therapy with or Without Orteronel
Authors: Primo N. Lara Jr, Edward Mayerson, Erik Gertz, Catherine Tangen, Amir Goldkorn, Marta van Loan, Maha Hussain, Shilpa Gupta, Jingsong Zhang, Mamta Parikh, Przemyslaw Twardowski, David I. Quinn, Michael LeBlanc, Nicholas J. Vogelzang, Ian Thompson, Neeraj Agarwal
Journal: European Urology (2023)
A homologous and molecular dual-targeted biomimetic nanocarrier for EGFR-related non-small cell lung cancer therapy
Authors: Bin Xu, Fanjun Zeng, Jialong Deng, Lintong Yao, Shengbo Liu, Hengliang Hou, Yucheng Huang, Hongyuan Zhu, Shaowei Wu, Qiaxuan Li, Weijie Zhan, Hongrui Qiu, Huili Wang, Yundong Li, Xianzhu Yang, Ziyang Cao, Yu Zhang, Haiyu Zhou
Journal: Bioactive Materials (2023)

The abnormal activation of epidermal growth factor receptor (EGFR) drives the development of non-small cell lung cancer (NSCLC). The EGFR-targeting tyrosine kinase inhibitor osimertinib is frequently used to clinically treat NSCLC and exhibits marked efficacy in patients with NSCLC who have an EGFR mutation. However, free osimertinib administration exhibits an inadequate response in vivo, with only ∼3% patients demonstrating a complete clinical response. Consequently, we designed a biomimetic nanoparticle (CMNP@Osi) comprising a polymeric nanoparticle core and tumor cell-derived membrane-coated shell that combines membrane-mediated homologous and molecular targeting for targeted drug delivery, thereby supporting a dual-target strategy for enhancing osimertinib efficacy. After intravenous injection, CMNP@Osi accumulates at tumor sites and displays enhanced uptake into cancer cells based on homologous targeting. Osimertinib is subsequently released into the cytoplasm, where it suppresses the phosphorylation of upstream EGFR and the downstream AKT signaling pathway and inhibits the proliferation of NSCLC cells. Thus, this dual-targeting strategy using a biomimetic nanocarrier can enhance molecular-targeted drug delivery and improve clinical efficacy.
Chitosan-based hydrogels for wound healing: Correspondence
Authors: Ali Alnazza Alhamad, Soumeia Zeghoud, Ilham Ben Amor, Hadia Hemmami
Journal: International Journal of Surgery (2023)

Alhamad, Ali Alnazza; Zeghoud, Soumeia; Amor, Ilham Ben; Hemmami, Hadia Author Information
Optimal postoperative surveillance strategies for cancer survivors with gastric neuroendocrine carcinoma based on individual risk: a multicenter real-world cohort study
Authors: Bin-bin Xu, Xin-Yang He, Yan-bing Zhou, Qing-liang He, Yan-tao Tian, Han-kun Hao, Xian-tu Qiu, Li-xin Jiang, Gang Zhao, Zhi li, Yan-chang Xu, Wei-hua Fu, Fang-qin Xue, Shu-liang Li, Ze-kuan Xu, Zheng-gang Zhu, Yong Li, En Li, Jin-ping Chen, Hong-lang Li, Li-sheng Cai, Dong Wu, Ping Li, Chao-hui Zheng, Jian-wei Xie, Jun Lu, Chang-Ming Huang
Journal: International Journal of Surgery (2023)

Background: The best follow-up strategy for cancer survivors after treatment should balance the effectiveness and cost of disease detection while detecting recurrence as early as possible. Due to the low incidence of gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma [G-(MA)NEC], high-level evidence-based follow-up strategies is limited. Currently, there is a lack of consensus among clinical practice guidelines regarding the appropriate follow-up strategies for patients with resectable G-(MA)NEC. Materials and methods: The study included patients diagnosed with G-(MA)NEC from 21 centers in China. The random forest survival model simulated the monthly probability of recurrence to establish an optimal surveillance schedule maximizing the power of detecting recurrence at each follow-up. The power and cost-effectiveness were compared with the National Comprehensive Cancer Network, European Neuroendocrine Tumor Society, and European Society for Medical Oncology Guidelines. Results: A total of 801 patients with G-(MA)NEC were included. The patients were stratified into four distinct risk groups utilizing the modified TNM staging system. The study cohort comprised 106 (13.2%), 120 (15.0%), 379 (47.3%), and 196 cases (24.5%) for modified groups IIA, IIB, IIIA, and IIIB, respectively. Based on the monthly probability of disease recurrence, the authors established four distinct follow-up strategies for each risk group. The total number of follow-ups 5 years after surgery in the four groups was 12, 12, 13, and 13 times, respectively. The risk-based follow-up strategies demonstrated improved detection efficiency compared to existing clinical guidelines. Further Markov decision-analytic models verified that the risk-based follow-up strategies were better and more cost-effective than the control strategy recommended by the guidelines. Conclusions: This study developed four different monitoring strategies based on individualized risks for patients with G-(MA)NEC, which may improve the detection power at each visit and were more economical, effective. Even though our results are limited by the biases related to the retrospective study design, we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending follow-up strategies for G-(MA)NEC.
Impact of delayed screening invitations on screen-detected and interval cancers in the Dutch colorectal cancer screening programme: individual-level data analysis
Authors: Esther Toes-Zoutendijk, Lucie de Jonge, Carola Adriana van Iersel, Manon C W Spaander, Anneke J van Vuuren, Folkert van Kemenade, Christian R Ramakers, Evelien Dekker, Iris D Nagetaal, Monique E van Leerdam, Iris Lansdorp-Vogelaar
Journal: Gut (2023)

Objective To assess the impact of delayed invitation on screen-detected and interval colorectal cancers (CRC) within a faecal immunochemical testing (FIT)-based CRC screening programme. Design All individuals that participated in 2017 and 2018 with a negative FIT and were eligible for CRC screening in 2019 and 2020 were included using individual-level data. Multivariable logistic regression analyses were used to assess the association between either the different time periods (ie, ‘ before ’, ‘ during ’ and ‘ after ’ the first COVID-19 wave) or the invitation interval on screen-detected and interval CRCs. Results Positive predictive value for advanced neoplasia (AN) was slightly lower during (OR=0.91) and after (OR=0.95) the first COVID-19 wave, but no significant difference was observed for the different invitation intervals. Out of all individuals that previously tested negative, 84 (0.004%) had an interval CRC beyond the 24 months since their last invitation. The time period of invitation as well as the extended invitation interval was not associated with detection rates for AN and interval CRC rate. Conclusion The impact of the first COVID-19 wave on screening yield was modest. A very small proportion of the FIT negatives had an interval CRC possibly due to an extended interval, which potentially could have been prevented if they had received the invitation earlier. Nonetheless, no increase in interval CRC rate was observed, indicating that an extended invitation interval up to 30 months had no negative impact on the performance of the CRC screening programme and a modest extension of the invitation interval seems an appropriate intervention.
Preclinical pharmacokinetic and pharmacodynamic evaluation of dasatinib and ponatinib for the treatment of T-cell acute lymphoblastic leukemia
Authors: Satoshi Yoshimura, John C. Panetta, Jianzhong Hu, Lie Li, Yoshihiro Gocho, Guoqing Du, Akihiro Umezawa, Seth E. Karol, Ching-Hon Pui, Charles G. Mullighan, Marina Konopleva, Wendy Stock, David T. Teachey, Nitin Jain, Jun J. Yang
Journal: Leukemia (2023)
Long COVID: pathophysiological factors and abnormalities of coagulation
Authors: Simone Turner, M. Asad Khan, David Putrino, Ashley Woodcock, Douglas B. Kell, Etheresia Pretorius
Journal: Trends in Endocrinology and Metabolism (2023)

Acute COVID-19 infection is followed by prolonged symptoms in approximately one in ten cases: known as Long COVID. The disease affects ~65 million individuals worldwide. Many pathophysiological processes appear to underlie Long COVID, including viral factors (persistence, reactivation, and bacteriophagic action of SARS CoV-2); host factors (chronic inflammation, metabolic and endocrine dysregulation, immune dysregulation, and autoimmunity); and downstream impacts (tissue damage from the initial infection, tissue hypoxia, host dysbiosis, and autonomic nervous system dysfunction). These mechanisms culminate in the long-term persistence of the disorder characterized by a thrombotic endothelialitis, endothelial inflammation, hyperactivated platelets, and fibrinaloid microclots. These abnormalities of blood vessels and coagulation affect every organ system and represent a unifying pathway for the various symptoms of Long COVID.
GSDMD in peripheral myeloid cells regulates microglial immune training and neuroinflammation in Parkinson's disease
Authors: Bingwei Wang, Yan Ma, Sheng Li, Hang Yao, Mingna Gu, Ying Liu, You Xue, Jianhua Ding, Chunmei Ma, Shuo Yang, Gang Hu
Journal: Acta Pharmaceutica Sinica B (2023)

Peripheral bacterial infections without impaired blood-brain barrier integrity have been attributed to the pathogenesis of Parkinson's disease (PD). Peripheral infection promotes innate immune training in microglia and exacerbates neuroinflammation. However, how changes in the peripheral environment mediate microglial training and exacerbation of infection-related PD is unknown. In this study, we demonstrate that GSDMD activation was enhanced in the spleen but not in the CNS of mice primed with low-dose LPS. GSDMD in peripheral myeloid cells promoted microglial immune training, thus exacerbating neuroinflammation and neurodegeneration during PD in an IL-1R-dependent manner. Furthermore, pharmacological inhibition of GSDMD alleviated the symptoms of PD in experimental PD models. Collectively, these findings demonstrate that GSDMD-induced pyroptosis in myeloid cells initiates neuroinflammation by regulating microglial training during infection-related PD. Based on these findings, GSDMD may serve as a therapeutic target for patients with PD.
Retraction Note: miR-195-5p/NOTCH2-mediated EMT modulates IL-4 secretion in colorectal cancer to affect M2-like TAM polarization
Authors: Xiaobin Lin, Shuyi Wang, Min Sun, Chunxiao Zhang, Chen Wei, Chaogang Yang, Rongzhang Dou, Qing Liu, Bin Xiong
Journal: Journal of Hematology & Oncology (2023)
Interactions between the lipidome and genetic and environmental factors in autism
Authors: Chloe X. Yap, Anjali K. Henders, Gail A. Alvares, Corey Giles, Kevin Huynh, Anh Nguyen, Leanne Wallace, Tiana McLaren, Yuanhao Yang, Leanna M. Hernandez, Michael J. Gandal, Narelle K. Hansell, Dominique Cleary, Rachel Grove, Claire Hafekost, Alexis Harun, Helen Holdsworth, Rachel Jellett, Feroza Khan, Lauren P. Lawson, Jodie Leslie, Mira Levis Frenk, Anne Masi, Nisha E. Mathew, Melanie Muniandy, Michaela Nothard, Jessica L. Miller, Lorelle Nunn, Lachlan T. Strike, Gemma Cadby, Eric K. Moses, Joseph Hung, Jennie Hui, John Beilby, Greig I. de Zubicaray, Paul M. Thompson, Katie L. McMahon, Margaret J. Wright, Peter M. Visscher, Paul A. Dawson, Cheryl Dissanayake, Valsamma Eapen, Helen S. Heussler, Andrew J. O. Whitehouse, Peter J. Meikle, Naomi R. Wray, Jacob Gratten
Journal: Nature Medicine (2023)

Autism omics research has historically been reductionist and diagnosis centric, with little attention paid to common co-occurring conditions (for example, sleep and feeding disorders) and the complex interplay between molecular profiles and neurodevelopment, genetics, environmental factors and health. Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis (n = 8), sleep disturbances (n = 20) and cognitive function (n = 8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster. We explored the interplay of environmental factors with neurodevelopment and the lipidome, finding that sleep disturbances and unhealthy diet have a convergent lipidome profile (with potential mediation by the microbiome) that is also independently associated with poorer adaptive function. In contrast, ASD lipidome differences were accounted for by dietary differences and sleep disturbances. We identified a large chr19p13.2 copy number variant genetic deletion spanning the LDLR gene and two high-confidence ASD genes (ELAVL3 and SMARCA4) in one child with an ASD diagnosis and widespread low-density lipoprotein-related lipidome derangements. Lipidomics captures the complexity of neurodevelopment, as well as the biological effects of conditions that commonly affect quality of life among autistic people.
PAUSE: principled feature attribution for unsupervised gene expression analysis
Authors: Joseph D. Janizek, Anna Spiro, Safiye Celik, Ben W. Blue, John C. Russell, Ting-I Lee, Matt Kaeberlin, Su-In Lee
Journal: Genome biology (2023)

As interest in using unsupervised deep learning models to analyze gene expression data has grown, an increasing number of methods have been developed to make these models more interpretable. These methods can be separated into two groups: post hoc analyses of black box models through feature attribution methods and approaches to build inherently interpretable models through biologically-constrained architectures. We argue that these approaches are not mutually exclusive, but can in fact be usefully combined. We propose PAUSE ( https://github.com/suinleelab/PAUSE ), an unsupervised pathway attribution method that identifies major sources of transcriptomic variation when combined with biologically-constrained neural network models.
Comprehensive response criteria for myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions: a proposal from the MLN International Working Group
Authors: William Shomali, Philomena Colucci, Tracy I. George, Jean-Jacques Kiladjian, Cheryl Langford, Jay L. Patel, Andreas Reiter, Alessandro M. Vannucchi, Jason Gotlib
Journal: Leukemia (2023)
AMPK is mitochondrial medicine for neuromuscular disorders
Authors: Andrew I. Mikhail, Sean Y. Ng, Stephanie R. Mattina, Vladimir Ljubicic
Journal: Trends in Molecular Medicine (2023)

Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1), and spinal muscular atrophy (SMA) are the most prevalent neuromuscular disorders (NMDs) in children and adults. Central to a healthy neuromuscular system are the processes that govern mitochondrial turnover and dynamics, which are regulated by AMP-activated protein kinase (AMPK). Here, we survey mitochondrial stresses that are common between, as well as unique to, DMD, DM1, and SMA, and which may serve as potential therapeutic targets to mitigate neuromuscular disease. We also highlight recent advances that leverage a mutation-agnostic strategy featuring physiological or pharmacological AMPK activation to enhance mitochondrial health in these conditions, as well as identify outstanding questions and opportunities for future pursuit.
Modeling cross‐talk of RNA modification enzymes reveals tumor microenvironment‐associated clinical significance and immunotherapy prediction in hepatobiliary malignancy
Authors: Feng Qi, Jia Li, Zhuoran Qi, Bin Zhou, Biwei Yang, Jun Zhang, Wenxing Qin
Journal: MedComm (2023)

RNA modification includes four main types, N6-methyladenosine, N1-methyladenosine, alternative polyadenylation (APA), and adenosine-to-inosine (A-to-I) RNA editing, involving 41 enzymes that serve as "writers", "readers" and "erasers". By collecting RNA modifying enzyme information in 1759 hepatobiliary malignancy (HBM) samples from 11 datasets, an RNA modification HBM Score (RH_score) was established based on unsupervised cluster analysis of RNA modification-associated differentially expressed genes (DEGs). We identified the imbalanced expression of 41 RNA modification enzymes in HBM, which was scientifically categorized into two groups: RH_Score high and RH_Score low. A high RH_Score was associated with a worse prognosis and more immature immune cells in the tumor microenvironment (TME), while a low RH_Score was associated with a better prognosis and more mature immune cells in the TME. Further analysis using single-cell databases showed that the high RH_Score was immune exhaustion in the TME. RH_Score was involved in transcriptional regulation and post-transcriptional events in HBM. Additionally, resistant and sensitive drugs were selected based on RNA modification, and anti-PD-L1 therapy responded better with low RH_Score. In conclusion, our study comprehensively analyzes RNA modification in HBM, which induces TME changes and transcriptional and posttranscriptional events, implying potential guiding significance in prognosis prediction and treatment options.
Improving and maintaining quality of hemodialysis in areas affected by war: a call to action!
Authors: Sami Alasfar, Hani Alashavi, Khaled Hajj Nasan, Abd Aljabbar Haj Mousa, Ismail Alkhatib, Rumeyza Kazancioglu, Mohamad Sekkarie, Saleh Kaysi, Mahmoud Daher, Lina Murad, Gilbert M. Burnham
Journal: Kidney International (2023)
Neuron-derived neuropeptide Y fine-tunes the splenic immune responses
Authors: Jinsong Yu, Ke Xiao, Xiaohua Chen, Lulu Deng, Lu Zhang, Yue Li, Anran Gao, Junjun Gao, Chengchao Wu, Xinmei Yang, Qiudi Zhou, Jian Yang, Chenyu Bao, Jiaji Jiao, Sheng Cheng, Zhiqing Guo, Weize Xu, Xiaojian Cao, Zheng Guo, Jinxia Dai, Ji Hu, Zhenfang Fu, Gang Cao
Journal: Neuron (2023)
VEGF Mediates Commissural Axon Chemoattraction through Its Receptor Flk1
Authors: Carmen Ruiz de Almodovar, Pierre J. Fabre, Ellen Knevels, Cathy Coulon, Inmaculada Segura, Patrick C.G. Haddick, Liesbeth Aerts, Nicolas Delattin, Geraldine Strasser, Won-Jong Oh, Christian Lange, Stefan Vinckier, Jody Haigh, Coralie Fouquet, Chengua Gu, Kari Alitalo, Valerie Castellani, Marc Tessier-Lavigne, Alain Chedotal, Frederic Charron, Peter Carmeliet
Journal: Neuron (2023)
The DAXX tax: C9orf72 DNA repeat expansions drive gain- and loss-of-function pathology in c9FTD/ALS
Authors: Feilin Liu, Wilfried Rossoll
Journal: Neuron (2023)

In this issue of Neuron, Liu et al. 1 Liu Y. Huang Z. Liu H. Ji Z. Arora A. Cai D. Wang H. Liu M. Simko E.A. Zhang Y. et al. DNA-initiated epigenetic cascades driven by C9orf72 hexanucleotide repeat. Neuron. 2023; 111: 1205-1221https://doi.org/10.1016/j.neuron.2023.01.022 Abstract Full Text Full Text PDF Scopus (4) Google Scholar identify DAXX as a C9orf72 hexanucleotide repeat expansion DNA-binding protein that initiates epigenetic modifications and chromatin remodeling, contributing to C9orf72 haploinsufficiency by inhibiting its stress-inducible expression and mediating both loss- and toxic gain-of-function pathology. In this issue of Neuron, Liu et al. 1 Liu Y. Huang Z. Liu H. Ji Z. Arora A. Cai D. Wang H. Liu M. Simko E.A. Zhang Y. et al. DNA-initiated epigenetic cascades driven by C9orf72 hexanucleotide repeat. Neuron. 2023; 111: 1205-1221https://doi.org/10.1016/j.neuron.2023.01.022 Abstract Full Text Full Text PDF Scopus (4) Google Scholar identify DAXX as a C9orf72 hexanucleotide repeat expansion DNA-binding protein that initiates epigenetic modifications and chromatin remodeling, contributing to C9orf72 haploinsufficiency by inhibiting its stress-inducible expression and mediating both loss- and toxic gain-of-function pathology. DNA-initiated epigenetic cascades driven by C9orf72 hexanucleotide repeatLiu et al.NeuronFebruary 22, 2023In BriefThis study has revealed pathogenic cascades initiated by C9orf72 hexanucleotide repeat DNA that influence genomic structures and gene expression. DAXX, a G4C2 repeat DNA-binding protein, regulates stress-dependent C9orf72 induction and global gene expression through chromatin remodeling and epigenetic changes as a key player mediating C9orf72 haploinsufficiency and DNA-dependent gain-of-function toxicities. Full-Text PDF
Dynamics of AMPA receptors regulate epileptogenesis in patients with epilepsy
Authors: Tsuyoshi Eiro, Tomoyuki Miyazaki, Mai Hatano, Waki Nakajima, Tetsu Arisawa, Yuuki Takada, Kimito Kimura, Akane Sano, Kotaro Nakano, Takahiro Mihara, Yutaro Takayama, Naoki Ikegaya, Masaki Iwasaki, Akitoyo Hishimoto, Yoshihiro Noda, Takahiro Miyazaki, Hiroyuki Uchida, Hideaki Tani, Nobuhiro Nagai, Teruki Koizumi, Shinichiro Nakajima, Masaru Mimura, Nozomu Matsuda, Kazuaki Kanai, Kazuhiro Takahashi, Hiroshi Ito, Yoji Hirano, Yuichi Kimura, Riki Matsumoto, Akio Ikeda, Takuya Takahashi
Journal: Cell Reports Medicine (2023)

The excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) contribute to epileptogenesis. Thirty patients with epilepsy and 31 healthy controls are scanned using positron emission tomography with our recently developed radiotracer for AMPARs, [11C]K-2, which measures the density of cell-surface AMPARs. In patients with focal-onset seizures, an increase in AMPAR trafficking augments the amplitude of abnormal gamma activity detected by electroencephalography. In contrast, patients with generalized-onset seizures exhibit a decrease in AMPARs coupled with increased amplitude of abnormal gamma activity. Patients with epilepsy had reduced AMPAR levels compared with healthy controls, and AMPARs are reduced in larger areas of the cortex in patients with generalized-onset seizures compared with those with focal-onset seizures. Thus, epileptic brain function can be regulated by the enhanced trafficking of AMPAR due to Hebbian plasticity with increased simultaneous neuronal firing and compensational downregulation of cell-surface AMPARs by the synaptic scaling.